From the TMS Board > Board News > Announcing PKC412 (Midostaurin) Trial
Announcing Novartis trial for PKC412 (Midostaurin), New Drug for Aggressive Mastocytosis
By Val Slee, TMS Co-Chair
(April 23, 2008) I received a call today from Leslie Fields, the Patient Advocate from Novartis, who is working to coordinate the opening of the study for PKC412 (Midostaurin). I have some details, although not all of them, but I wanted to share what I know for those of you who are anxiously waiting for information. She did not have the inclusion and exclusion criteria yet.
- This will be an open label study, single-arm phase, so all patients will get the drug, and no patient will get a placebo.
- There will be a year of recruitment, starting in August in the United States, and a year "on study."
- For those patients that have good results on the drug, therapy will be continued for compassionate use.
- There will be inclusion and exclusion criteria, but again, I do not have them yet.
- The current sites in the US will be at UCLA, the Oregon Science Center, and the University of Colorado.
- This will be a global trial, and the other sites that will be involved will be: France, Germany, Italy, Austria, Canada, Australia, and the UK.
Ms. Fields does not yet have the details about costs involved for the patient, and she did not know yet if transportation to the centers could be covered. Those details will be available later.
I will be in touch with Ms. Fields, and we will work together on making this information available to all patients with aggressive mastocytosis.
More Information on PKC412 (Midostaurin)
From Novartis’s Web Site: PKC 412 — Inhibiting multiple signal transduction pathways
"Protein kinase C412 (Midostaurin) is an oral multitargeted kinase inhibitor. It potently inhibits the FLT-3 receptor tyrosine kinase, which is mutated in approximately one third of acute myelogenous leukemia (AML) patients, and is implicated in poor prognosis. It also inhibits multiple other molecular targets thought to be important for the pathogenesis of AML. These targets include VEGFR-2, platelet-derived growth- factor receptor (PDGFR), c-KIT, and the Pgp-mediated multidrug resistance gene MDR. In a Phase IB study of Midostaurin in combination with daunorubicin and cytarabine, 11 of 12 (92%) patients with newly diagnosed FLT-3 mutated AML had a complete response.
"In addition to the above targets, Midostaurin inhibits multiple isoforms of the serine/ threonine PKC. In p reclinical studies, Midostaurin showed broad antiproliferative activity against various tumor cell lines, including those that were resistant to several other chemotherapeutic agents.
"Midostaurin is now being investigated in Phase III trials in AML."
Source URL: Novartis Oncology Products in Development.
Rationale for PKC412 Treatment
"Patients with ISM [indolent systemic mastocytosis] are treated with ‘mediator-targeting’ drugs, whereas patients with ASM [aggressive systemic mastocytosis] or MCL [mast cell leukemia] are candidates for cytoreductive therapy. The use of ‘KIT-targeting’ tyrosine kinase (TK) inhibitors has also been suggested. Unfortunately, the D816V KIT mutation is associated with resistance against imatinib [Gleevec]. However, several second-generation TK inhibitors, such as PKC412 (midostaurin), AMN107 (nilotinib), or BMS354825 (dasatinib) are available and reportedly inhibit growth of MCs carrying KIT D816V. These drugs might be useful for therapy of ASM or MCL in the future."
From abstract to chapter by Dr. Peter Valent in Rare Hematological Malignancies, edited by Stephen M. Ansell, SpringerLink, 2008, pp. 399-419 [DOI: 10.1007/978-0-387-73744-7, ISBN: 978-0-387-73743-0 (Print) 978-0-387-73744-7 (Online), URL].
Page last updated: April 24, 2008